Modomics - A Database of RNA Modifications

Published on Oct. 1, 2018 in EMBO J volume 37(19).

PubMed ID: 30087110

DOI: embj.201694813


Epitranscriptomic events such as adenosine-to-inosine (A-to-I) RNA editing by ADARcan recode mRNAs to translate novel proteins. Editing of the mRNA that encodes actincrosslinking protein Filamin A (FLNA) mediates a Q-to-R transition in theinteractive C-terminal region. While FLNA editing is conserved among vertebrates,its physiological function remains unclear. Here, we show that cardiovasculartissues in humans and mice show massive editing and that FLNA RNA is the mostprominent substrate. Patient-derived RNA-Seq data demonstrate a significant drop inFLNA editing associated with cardiovascular diseases. Using mice with only impairedFLNA editing, we observed increased vascular contraction and diastolic hypertensionaccompanied by increased myosin light chain phosphorylation, arterial remodeling,and left ventricular wall thickening, which eventually causes cardiac remodeling andreduced systolic output. These results demonstrate a causal relationship between RNAediting and the development of cardiovascular disease indicating that a singleepitranscriptomic RNA modification can maintain cardiovascular health.CI - © 2018 The Authors. Published under the terms of the CC BY 4.0 license.